IM CNS

• Leydig (interstitial) cells


  Secrete testosterone and estradiol
• Seminiferous tubules


  Produce sperm
• Regulation of testes


  1. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secreted by anterior pituitary

  2. Under influence of hypothalamic gonadotropin-releasing hormone (GnRH)
• LH stimulation of Leydig cells

  1. Secrete testosterone

  2. Negative feedback on pituitary and hypothalamus to inhibit further LH production
• FSH stimulation of Sertoli cells


  1. Sperm production

  2. Feedback inhibition through gonadal steroids and inhibin
• Biochemical evaluation of hypothalamic-pituitary-Leydig axis


  Measure serum LH and testosterone concentrations
• Evaluation of hypothalamic-pituitary seminiferous tubular axis


  Semen analysis and serum FSH determination
• Testing pituitary gonadotropin release


  GnRH stimulation
• Testing testicular testosterone secretion

  Injections of human chorionic gonadotropin (HCG)
• Hypogonadism is either testosterone deficiency or defective spermatogenesis
• Testosterone deficiency


  • Development of wolffian duct structures
  • Virilization of external genitalia
• Androgen deficiency during gestation


  • Micropenis
  • Cryptorchidism
• Androgen deficiency during puberty

  • Male sexual differentiation
  • Growth of scrotum, epididymis, vas deferens, seminal vesicles, prostate, penis, skeletal muscle, larynx
  • Growth of axillary, pubic, facial, and body hair
  • Epiphyseal cartilage growth and fusion
• Prepubertal androgen deficiency


  • Poor muscle development
  • Decreased strength and endurance
  • High-pitched voice
  • Sparse axillary and pubic hair
  • Absence of facial and body hair
  • Eunuchoid proportions
• Postpubertal androgen deficiency


  • Decreased libido
  • Impotence
  • Low energy
  • Fine wrinkling around eyes and mouth
  • Diminished facial and body hair
• Categories of male hypogonadism


  • Primary or hypergonadotropic hypogonadism
  • Secondary or hypogonadotropic hypogonadism
  • Defects in androgen action
• Primary or hypergonadotropic hypogonadism


  Defect in testes, characterized by oligospermia/azoospermia and low testosterone with elevated LH and FSH
• Secondary or hypogonadotropic hypogonadism


  Defect in hypothalamus or pituitary, characterized by low testosterone or ineffective spermatogenesis due to inadequate gonadotropins
• Hypogonadism from defects in androgen action


  Third category of hypogonadism
• Causes of hypothalamic-pituitary disorders


  • Panhypopituitarism
  • Isolated gonadotropin deficiency
  • Complex congenital syndromes
  • Hyperprolactinemia
  • Hypothalamic dysfunction
• Kallmann syndrome


  Hypogonadotropic hypogonadism with olfactory deficits, results from GnRH neuron migration defect
• Hyperprolactinemia


  Inhibits GnRH release, LH effectiveness, and testosterone actions, reversible with normalization of prolactin
• Hypothalamic dysfunction


  Secondary hypogonadism from weight loss or systemic illness, defect in GnRH release
• Klinefelter's syndrome


  Most common congenital cause of primary testicular failure, XXY genotype
• Klinefelter's syndrome


  • Variable hypogonadism
  • Gynecomastia
  • Small, firm testes
  • Azoospermia
  • Eunuchoid proportions
  • Elevated FSH and LH
• Myotonic dystrophy


  Congenital condition with primary gonadal failure
• Cryptorchidism


  Failure of testicular descent, leads to defective spermatogenesis but normal Leydig cell function
• Bilateral anorchia


  Vanishing testicle syndrome, full external genitalia but absent testicular tissue
• Primary gonadal failure


  • Found in patients with myotonic dystrophy
  • Characterized by progressive weakness, atrophy of facial/neck/hand/lower extremity muscles, frontal baldness, and myotonia
• Cryptorchidism


  Condition where testes are maintained in the intraabdominal position, leading to defective spermatogenesis and oligospermia. Leydig cell function usually remains normal, resulting in normal levels of adult testosterone.
• Bilateral anorchia (vanishing testicle syndrome)


  Rare condition where testicular tissue disappears before or shortly after birth, resulting in an empty scrotum. Differentiated from cryptorchidism by HCG stimulation test.
• Causes of acquired gonadal failure


  • Infections (mumps, gonococcal or lepromatous orchitis)
  • Irradiation
  • Vascular injury
  • Trauma
  • Alcohol ingestion
  • Chemotherapeutic drugs (especially alkylating agents)
• Serum FSH concentration in acquired gonadal failure

  May be normal or elevated, depending on the degree of damage to the seminiferous tubules
• Leydig cell compartment in acquired gonadal failure


  May also be damaged by the same conditions
• Gradual decline in testicular function with age


  Possibly due to microvascular insufficiency
• Serum LH concentration in decreased testosterone production


  Usually elevated
• Androgen action


  When testosterone or DHT binds to the androgen receptor in target cells, the receptor is activated and binds DNA, stimulating transcription, protein synthesis, and cell growth
• Testicular feminization (male pseudohermaphroditism)


  Caused by absence of androgen receptors. Genetic males have cryptorchid testes but appear to be phenotypic females.
• Testicular feminization


  • Labial-scrotal folds fail to fuse, resulting in a short vagina
  • Fallopian tubes, uterus, and upper portion of the vagina are absent
  • Breast enlargement at puberty due to testes secreting estradiol and peripheral tissues converting testosterone/adrenal androgens to estrogens
  • Axillary and pubic hair does not grow due to lack of androgen action
• Serum testosterone concentrations in testicular feminization


  Elevated due to continuous stimulation by elevated LH